We have continued our search for age-dependent alterations in the physico-chemical structure of chromatin. Our approach has been to investigate a specific non-histone chromatin protein, the T3-hormone receptor. This receptor protein is known to be essential for proper control of several specific liver enzymes and can be related potentially to general physiological processes known to change with age. Results using liver tissue from Sprague Dawley rats of ages 8 to 32 months show a slight but statistically significant decrease in the number of T3 binding sites but no change in binding affinity. Old hypophysectomized animals have been shown by other laboratories to undergo some rejuvenation-like changes, and we have also found some evidence for the regeneration of the kidney glomerular region according to electron microscopy analysis. However, the old hypophysectomized animals do not show a return of T3 receptor levels in the liver to that of young animals. The effects of T3 administration to C57BL/6J mice on the number of nucleoli and ribosomal RNA gene dosage has been investigated. Although nucleoli number was increased up to 50%, no effect on ribosomal gene dosage was evident.